Importance Despite lack of evidence of their utility, biomarkers of ovarian reserve are being promoted as potential markers of reproductive potential or “fertility tests.” Objective To determine the extent to which biomarkers of ovarian reserve are associated with reproductive potential among late-reproductive age women. Design, Setting, and Participants Prospective, time-to-pregnancy cohort study (2008-March 2016) of women (N=981) 30–44 years of age without a history of infertility who had been trying to conceive for 3 months or less were recruited from the community in the Raleigh-Durham area. Exposures Early follicular phase serum level of antimüllerian hormone (AMH), follicle stimulating hormone (FSH), and inhibin B, and urinary level of FSH. Main Outcomes and Measures The primary outcomes were the cumulative probability of conception by 6 and 12 cycles of attempt and relative fecundability, the probability of conception in a given menstrual cycle. Conception was defined as a positive pregnancy test. Results 750 women (33.3[3.2] years of age; 77% white; 36% overweight or obese), provided a blood and urine sample and were included in the analysis. After adjusting for age, body mass index, race, current smoking status and recent hormonal contraceptive use, women with low AMH values (<0.7ng/ml, N=84) did not have a significantly different predicted probability of conceiving by 6 cycles of attempt (65%; 95% Confidence Interval (CI): 50–75%) compared to women (N=579) with normal values (62%; 95% CI: 57–66%) nor by 12 cycles of attempt (84%; 95% CI: 70–91% versus 75%; 95% CI: 70–79%, respectively). Women with high serum FSH values (>10mIU/ml, N=83) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (63%; 95% CI: 50–73%) compared to women (N=654) with normal values (62%; 95% CI: 57–66%) nor after 12 cycles of attempt (82%; 95% CI: 70–89 versus 75%; 95% CI: 70–78%). Women with high urinary FSH values (>11.5mIU/mgcr, N=69) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (61%; 95% CI: 46–74%) compared to women (N=660) with normal values (62%; 95% CI: 58–66%) nor after 12 cycles of attempt (70%; 95% CI: 54–80% versus 76%; 95% CI: 72–80%). Inhibin b levels (N=737) were not associated with the probability of conceiving in a given cycle (Hazard Ratio [per 1pg/ml increase] = 0.999; 95% CI: 0.997–1.001). Conclusions Among women age 30–44 years of age without a history of infertility, who had been trying to conceive for 3 months or less, biomarkers indicating diminished ovarian reserve, compared to normal ovarian reserve, were not associated with reduced fertility. These findings do not support the use of urinary or blood FSH tests or AMH levels to assess natural fertility for women with these characteristics.

Objective To generate estimates of the association between markers of ovarian aging and natural fertility in a community sample at risk for ovarian aging. Methods Women aged 30–44 years with no history of infertility who had been trying to conceive for less than 3 months provided early-follicular phase serum and urine (N=100). Subsequently, these women kept a diary to record menstrual bleeding and intercourse and conducted standardized pregnancy testing for up to 6 months. Serum was analyzed for estradiol, follicle-stimulating hormone (FSH), antimüllerian hormone, and inhibin B. Urine was analyzed for FSH and estrone 3-glucuronide (E13G). Diary data on menstrual cycle day and patterns of intercourse were used to calculate day-specific fecundability ratios. Results Sixty-three percent of subjects conceived within 6 months. After adjusting for age, 18 women (18%) with serum antimüllerian hormone levels of 0.7 ng/ml or less had significantly reduced fecundability given intercourse on a fertile day compared to women with higher antimüllerian hormone levels (fecundability ratio 0.38, 95% CI:0.08–0.91). The day-specific fecundability for women with early-follicular phase serum FSH values greater than 10 mIU/ml compared to women with lower FSH levels was also reduced, though nonsignificantly (11% of women affected; fecundability ratio 0.44, 95% CI: 0.08, 1.10). The association with urinary FSH was weaker (27% women affected; fecundability ratio 0.61, 95% CI: 0.26, 1.26), and the associations for the other markers were weaker still. Conclusions Early-follicular phase antimüllerian hormone appears to be associated with natural fertility in the general population.